POS1230 INCREASED ANTIBODY RESPONSE AFTER SARS-CoV-2 mRNA-BASED VACCINATION IN RITUXIMAB-TREATED PATIENTS WITH PREVIOUS COVID-19 INFECTION
Authors: J. Avouac, R. Ghossan, O. Al Tabaa, A. Combier, A. Steelandt, M. Thomas, O. Fogel, A. A. Mariaggi, J. F. Meritet, F. Rozenberg, A. Moltó, C. Miceli Richard, Y. Allanore
Journal: Annals of the Rheumatic Diseases (2022)

Background Rituximab (RTX) is associated with reduced humoral response to SARS-CoV-2 mRNA-based vaccine (1, 2). A recent study has shown that, despite their immunosuppression burden, kidney transplant recipients with previous exposure to SARS-CoV-2 showed a marked increase in antibody titer, even after a single dose of vaccine (3). Objectives To describe the results of immunization after 1 to 3 doses of mRNA SARS-CoV-2 vaccine in RTX-treated patients with previous symptomatic COVID-19 infection. Methods Observational prospective usual care study including consecutive patients with inflammatory rheumatic diseases in maintenance therapy with RTX. All patients received a 1 to 3-dose regimen of mRNA-based COVID-19 vaccination (BNT162b2 Pfizer/BioNTech or mRNA-1273, Moderna). Serum IgG antibody levels against SARS-CoV-2 spike proteins were measured at the time of the new RTX infusion. The SARS-CoV-2 S1/S2 IgG immunoassay (DiaSorin) was used for the quantitative determination of antibodies to the receptor-binding domain of the viral spike (S) protein. Seropositivity was defined by anti-S antibodies &gt;15 UA/mL. Results We included 69 patients (60 females, mean age 60±13 years) on maintenance therapy with RTX including 13 with previous symptomatic COVID-19, all proven by RT-PCR (10 females, mean age 58±12 years) (Table 1). SymptomaticCOVID-19 occurred between March 2020 and May 2021. The mean interval between the infection and vaccination was 8±3 months and the serological response was assessed after a mean of 74±58 days from the last dose of vaccination (3 rd dose for 3 patients, 2 nd dose for 6 patients and 1 st dose for 4 patients). The 56 patients with no history of symptomatic COVID-19 infection all received 3 doses of vaccine and the serological response was assessed after a mean of 63±27 days from the 3 rd dose of vaccination. The seropositivity rate was significantly higher in RTX-treated patients with previous symptomatic COVID-19 infection (11/13, 85% vs.15/56, 27%, p&lt;0.001). Anti-S antibody titles were also markedly increased in patients with previous symptomatic COVID-19 infection (median 119 AU/mL, 95% CI 16-400 AU/mL vs. 3.80 AU/mL, 95% CI 3.80-4.81 AU/mL p&lt;0.0001) (Figure 1). Antibody titles were not different according to the severity of previous COVID-19, the number of doses of vaccine, the underlying disease, and B-cell counts. Table 1. Study population Patients with previous symptomatic COVID-19 (n=13 ) Patients without symptomatic COVID-19 (n=56 ) Age (years), mean ± SD 58±12 60±11 Females, n (%) 10 (77) 50 (89) Underlying disease: Rheumatoid arthritis 10 (77) 45 (80) Systemic sclerosis 2 (15) 5 (9) Systemic lupus erythematosus 1 (8) 1 (2) Sjögren syndrome 0 (0) 3 (5) Mixed connective tissue disease 0 (0) 2 (4) Disease duration (years), mean ± SD 17±9 20±10 Associated Methotrexate, n (%) 9 (69) 36 (64) Current treatment with corticosteroids, n (%) 5 (38) 21 (38) Corticosteroid dose &gt;10 mg/day, n (%) 0 (0) 0 (0) CD19+ (/µL) (100-600), mean ± SD 65±106 45±51 CD19 &lt;18/µL, n (%) 7 (54) 33 (58) Figure 1. Distribution of SARS-CoV-2 spike antibody levels according to the history of proven symptomatic COVID-19. **** p&lt;0.0001 by Mann Whitney test. Dotted red line corresponds to the seropositivity threshold Conclusion RTX-treated patients with previous proven COVID-19 showed increased seropositivity and antibody titers after SARS-CoV-2 vaccination, even after a single-dose of vaccine. This response is strikingly different from that observed for SARS-CoV-2-naïve RTX treated patients who received 3 doses of SARS-CoV-2 mRNA-based vaccination. An “antigen dose phenomenon” may account for these discrepancies. A potential clinical implication might be to increase antibody response with an additional dose of vaccine following an exposure to SARS-CoV-2 in RTX-treated patients with absent or insufficient postvaccination antibody response. References [1] Avouac et al, Rheumatology 2021 [2] Jyssum et al, Lancet Rheumatol 2021 [3] Benotmane et al, Am J Transplant 2021 Disclosure of Interests None declared